Tail-suspended Rat Research Articles

Small Animal Model of Weightlessness for Pharmacokinetic Evaluation

As the United States seeks a greater presence in space, physiologic changes associated with space flight become of greater concern. Exposure to a weightless environment has been shown to have numerous effects on body composition and organ function. Alterations include decreases in muscle and liver mass, changes in bone structure and integrity, and fluid shifts markedly affecting cardiovascular functioning. Furthermore, metabolic activity of the liver has been found to be altered in rats after extended periods of weightlessness. As the length of space travel increases, the probability for the need to administer pharmacologic agents to crew members during space flight for prophylaxis or treatment becomes greater. Thus, because of the observed physiologic and metabolic changes associated with weightlessness, it is reasonable to assume that the pharmacokinetics and pharmacodynamics of xenobiotics administered during space flight may be different that those found in 1g environment. To address these possible changes, the development of a model of weightlessness to investigate possible alterations in drug pharmacokinetics and pharmacodynamics before space flight is of importance. The tail-suspended rat is a well-described model of weightlessness. During the time of the suspension, the pharmacokinetics of marker compounds can be used to evaluate changes in hepatic and renal physiology. Rats suspended for different periods allow for the investigation of the length of weightlessness exposure and drug pharmacology. Results from the use of the suspended rat model provide valuable information regarding possible pharmacokinetic and pharmacodynamic changes associated with weightlessness, and therefore, provide space biomedical researchers with a method of investigating drug administration during space flight missions.

The pituitary: Aging and spaceflown rats

Decrements in growth hormone (GH) release we observed in two spaceflight experiments and four tail-suspended rat studies mimic age-associated changes in the mammalian pituitary GH system seen by Meites and others. The spaceflight data suggest that formation of high molecular weight bioactive disulfide-linked aggregates of the 20 and 22K monomeric GH forms may be reduced in microgravity, thereby, reducing target tissue activity. Correlative studies to confirm spaceflight as a model for pituitary GH system aging should include: 1) investigation of mechanisms of intracellular hormone packaging, 2) consequences to biological activity of the hormone molecule, and 3) study of intracellular microtubule dynamics.

Effects of simulated weightlessness on bone properties in rats

This paper addresses two questions: (1) are reductions in bone apposition rate during disuse due to increased periods of ‘resting’ during bone formation? and (2) are diaphyseal strength changes due to disuse caused by changes in the quality as well as the quantity of the bone matrix? These problems were studied using the tail-suspended rat model. Seventy 210 g female Sprague-Dawley rats were divided into control and suspended groups and studied for 1 or 2 weeks. Tetracycline labels at varying intervals were used to measure bone formation rates and to assess the duration of rest periods. The mechanical properties of the femoral midshaft, neck, and distal metaphysis, and of the proximal tibia, were studied. The composition of the entire femur and the geometry of the femoral midshaft were also analyzed, and beam theory was used to compare changes in these variables with those in bending strength. Contrary to previous findings in the tibia, suspension did not result in a decrease in the mean mineral apposition rate at the femur midshaft. Neither was there an effect on rest periods, so the answer to the first question was no, at least for the femur. Femur composition, cross-sectional geometry, and strength were significantly altered by disuse after 2 weeks, but not after 1 week. Femur mineralization was affected by time, but not by suspension, and bending yield stress was affected by suspension but not by time. Thus, the answer to the second question remains unclear, but is probably yes.